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Etoposide pharmacokinetics in children treated for acute myeloid leukemia

Josefine Palle1, Britt-Marie Frost, Frost Britt-Marie

  • 1Department of Women's and Children's Health, University Children's Hospital, Uppsala, Sweden. josefine.palle@akademiska.se

Anti-Cancer Drugs
|September 27, 2006
PubMed

Insights

Etoposide pharmacokinetics in children with acute myeloid leukemia showed no age-based dosing needs for infants over 3 months. Children with Down's syndrome may require dose adjustments, and consistent clearance suggests guided dosing could be beneficial.

Area of Science:

  • Pharmacology
  • Pediatric Oncology
  • Clinical Pharmacokinetics

Background:

  • Acute myeloid leukemia (AML) is a significant pediatric cancer.
  • Etoposide is a key chemotherapeutic agent used in AML treatment.
  • Understanding etoposide pharmacokinetics in children is crucial for optimizing therapy.

Purpose of the Study:

  • To investigate the pharmacokinetics of etoposide in pediatric patients with newly diagnosed AML.
  • To assess the influence of age and Down's syndrome on etoposide clearance.
  • To evaluate the inter-course variability of etoposide pharmacokinetics and its correlation with treatment outcomes.

Main Methods:

  • Etoposide administered via 96-hour continuous intravenous infusion (100 mg/m²/24h) to 45 children with AML.
  • Concomitant administration of cytarabine and 6-thioguanine.
  • Pharmacokinetic analysis of etoposide clearance, comparing age groups and children with/without Down's syndrome.
  • Assessment of correlation between etoposide pharmacokinetics and remission/relapse rates.

Main Results:

  • Median total body clearance of etoposide was similar across different age groups of children without Down's syndrome.
  • Children with Down's syndrome exhibited a trend towards lower etoposide clearance compared to non-Down's syndrome children.
  • Significant correlation observed in individual etoposide clearance values between treatment courses, indicating low variability.
  • No significant correlation found between etoposide pharmacokinetics and remission or relapse rates.

Conclusions:

  • Age-dependent pharmacokinetic differences do not support specific dose calculation guidelines for infants over 3 months old.
  • Children with Down's syndrome may benefit from etoposide dose reduction, pending further confirmation.
  • Low inter-course variability suggests that etoposide dosing guided by pharmacokinetics could be clinically valuable if efficacy and toxicity benefits are demonstrated in larger studies.

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